title: A bacterial phosphatase-like enzyme of the malaria parasite Plasmodium falciparum possesses tyrosine phosphatase activity and is implicated in the regulation of band 3 dynamics during parasite invasion.
abstract: Eukaryotic parasites of the genus Plasmodium cause malaria by invading and developing within host erythrocytes. Here, we demonstrate that PfShelph2, a gene product of Plasmodium falciparum that belongs to the Shewanella-like phosphatase (Shelph) subfamily, selectively hydrolyzes phosphotyrosine, as shown for other previously studied Shelph family members. In the extracellular merozoite stage, PfShelph2 localizes to vesicles that appear to be distinct from those of rhoptry, dense granule, or microneme organelles. During invasion, PfShelph2 is released from these vesicles and exported to the host erythrocyte. In vitro, PfShelph2 shows tyrosine phosphatase activity against the host erythrocyte protein Band 3, which is the most abundant tyrosine-phosphorylated species of the erythrocyte. During P. falciparum invasion, Band 3 undergoes dynamic and rapid clearance from the invasion junction within 1 to 2 s of parasite attachment to the erythrocyte. Release of Pfshelph2 occurs after clearance of Band 3 from the parasite-host cell interface and when the parasite is nearly or completely enclosed in the nascent vacuole. We propose a model in which the phosphatase modifies Band 3 in time to restore its interaction with the cytoskeleton and thus reestablishes the erythrocyte cytoskeletal network at the end of the invasion process.
authors.affiliation: Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, Indiana, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Fernandez-Pol
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Slouka
authors.forename: Souvik
authors.initials: S
authors.lastname: Bhattacharjee
authors.forename: Yana
authors.initials: Y
authors.lastname: Fedotova
authors.forename: Stefan
authors.initials: S
authors.lastname: Freed
authors.forename: Xiuli
authors.initials: X
authors.lastname: An
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Holder
authors.forename: Estela
authors.initials: E
authors.lastname: Campanella
authors.forename: Philip S
authors.initials: PS
authors.lastname: Low
authors.forename: Narla
authors.initials: N
authors.lastname: Mohandas
authors.forename: Kasturi
authors.initials: K
authors.lastname: Haldar
mesh_terms: D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism*; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D006790:Host-Parasite Interactions; D006801:Humans; D006868:Hydrolysis; D052940:Merozoites / Q000201:enzymology / Q000502:physiology; D019000:Phosphotyrosine / Q000378:metabolism; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000378:metabolism / Q000472:pathogenicity / Q000502:physiology; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism*
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D015800:Protozoan Proteins; D019000:Phosphotyrosine; D017027:Protein Tyrosine Phosphatases